The family of short trans-acting antisense RNA transcripts known as the microRNAs regulate target mRNAs via eliciting mRNA degradation or arrested translation. MicroRNAs are important in regulating prenatal brain development, and almost certainly have functions within the mature brain as well. We hypothesize that microRNAs participate in the regulation of human mRNAs, including those that are involved in the pathophysiology of psychiatric disorders. Although postmortem human brain samples have proven to be a valuable and unique resource for studying biochemical abnormalities that occur in depression and major psychoses, no methods for reliably measuring microRNAs have yet been reported for postmortem brain. In order to study the possible role of microRNA pathways in human disease, we aim to: 1) Validate methods of microRNA microarrays for measuring known human microRNAs within postmortem human brain. 2) Compare microRNA expression in prefrontal cortex across two different cohorts of postmortem brain samples including normal controls and a set of matched depressed subjects. The purpose of this proposal is to set the stage for genome-wide analysis of all known human microRNAs in samples of postmortem brain. This is the necessary first step towards our eventual goals: to learn which mRNA targets and neural pathways are regulated by microRNAs, and to learn whether any specific microRNAs show differential expression in subjects with psychiatric disorders. Our proposed study will yield important information on the neurobiology of depression and may indicate possible novel sites for therapeutic interventions, which may eventually lead to better treatment and possibly prevention of depression. [unreadable] [unreadable] [unreadable]